The long range objective of this project is to carefully re-examine the nature of binding specificity at antibody combining regions and other types of receptor sites. The effects of polyvalent binding on binding energy and specificity will be considered, and together these properties will be related to the behavior of immune systems. In particular, multispecific binding of disparate structures by individual antibody species is being studied through screening of specifically purified, radiolabeled antibodies with affinity chromatography column. The ligands are bound to these columns using large haptenic reagents synthesized specially for this purpose using methods of peptide synthesis. Multispecific binding will be used for producing and isolating homogeneous antibody by cross-stimulation and immunoadsorption. The resulting preparations will be studied by amino acid sequencing in order to gain more insight into the nature of antibody diversity. Methods for improving sequence analysis are actively being pursued. BIBLIOGRAPHIC REFERENCES: Inman, J.K. The antibody combining region: Speculations on the hypothesis of general multispecificity. In Bell, G.I., Perelson, A.S. and Pimbley, G.G. (Eds.). Theoretical Immunology, Marcel Dekker, Inc., N.Y. In press, 1977. Merchant, B. and Inman, J.K. Hapten-specific hemolytic plaque assays usually fail to detect most of the diversity in the anti-hapten response. J. Exp. Med. 145: 372-389, 1977.